Sepsis and septic shock related to invasive bacterial infection are associated with a high lethality (1). Excessive release of host inflammatory mediators like tumor necrosis factor (TNF), contribute to the pathogenesis of sepsis (2). Inhibitors of these mediators, i.e. TNF soluble receptor, TNFsr, have been shown to improve survival in preclinical animal models of sepsis (2), but were not effective in humans. One explanation for this discrepancy was that concurrent therapies like intravenous fluids and vasopressors, routinely applied to humans during illness, were not used in the animal models. While frequently including antibiotic use, preclinical studies rarely employ such hemodynamic treatments. This may have influenced the efficacy of the agents used to counteract the inflammatory response to sepsis (3, 4). Preclinical and clinical data show that fluid treatment suppresses inflammatory cytokine release during hemorrhage and trauma (5) and in response to a lipopolysaccharide challenge (6). Weve shown in a rat sepsis model that both fluid and a selective TNF inhibitor when applied separately, are protective and improve survival. However, when combined, the observed effect on decreasing mortality is significantly less than would be estimated from their individual ones. Fluid administration also appeared to reduce circulating TNF levels. To date, the potential immunomodulatory effects of normal saline infusion have not been investigated in a preclinical sepsis model. The present study will investigate the effects of fluid administration and TNFsr treatment alone or together on peripheral blood mononuclear cell inflammatory cytokine and cytokine receptor gene expression employing reverse transcriptase-polymerase chain reaction (RT-PCR) superarrays as well as on levels of circulating cellular (leukocytes) and molecular (cytokine panels) inflammatory mediators and on bacterial clearance. At this time, an initial set of experiments have been completed and RT-PCR superarrays are under analysis.